Study On The Reactions Of Introducing Fluorine-containing Functional Groups Into Aryl-substituted Ethylenes And Heterocycles

Fluorine is the most oxidizing and chemically active element.Fluorine is also the most electronegative element in the periodic table.Due to these special characteristics of fluorine,the introduction of fluorine into the molecules can significantly change their physical,chemical and biological properties.Especially in the field of medicinal chemistry,the introduction of fluorine atoms or fluorine-containing functional groups into the lead compounds has become one of the important research strategies for drug structure optimization.Hence,in this thesis two fluorine-containing reagents were developed for the efficient methods for introducing fluorine-containing functional groups into aryl-substituted ethylene and electron-rich nitrogen-containing aromatic heterocyclic.There are many ways to introduce fluorine into organic molecules,and trifluoromethylation of a substrate is a commonly used method.A difunctionalization reaction on aryl-substituted ethylene was explored by using of Langlois reagent(CF3SO2Na)as a trifluoromethylation reagent,tert-butyl nitrite(TBN)as an oxidant and oxime source.First,the reaction condition was screened,and the optimal condition was determined.Moreover,the generality of the reaction was examined.In addition,the structure of the product was confirmed is through X-ray diffraction experiments.Finally,it reaction mechanism was illustrated as a free radical process.The cheap and readily accessible trifluoromethylation reagent,the mile reaction condition as well as transition metal free catalysis make this to be a good protocol for the synthesis of α-trifluoromethyl ethyl ketoxime.Then,the FeCl3 promoted direct trifluoromethylselenylation reaction of electron-rich nitrogen-containing aromatic heterocyclic compounds was developed with p-toluenesulfonyl trifluoromethylselenyl ether(TsSeCF3)as a trifluoroselenyl reagent.By screening the reaction conditions,the optimal condition for the reaction was determined.Moreover,the substrate scope of this reaction was broad and t the reaction mechanism was studied which may be electrophilic substitution.In this reaction,the trifluoroselenyl reagent is stable and easy to store,and the reaction conditions are mild and environmentally friendly.It provides a new route for the synthesis of trifluoroselenyl indole and other nitrogen-containing aromatic heterocyclic compounds.In summary,we have developed two new methods for effective and selective trifluoromethylation or trifluoromethylselenylation of organic molecules,which provide new methods for the introducing fluorine-contained groups to the drugs at late stage.